|Systematic (IUPAC) name|
|Trade names||Adipex-p, Duromine, Metermine, Suprenza|
Recreational: oral, insufflation, intravenous
|Bioavailability||High (almost complete)|
|Protein binding||Approximately 96.3%|
|Biological half-life||25 hours, urinary pH-dependent|
|Excretion||Urinary (62–85% unchanged)|
|ATC code||A08AA01 (WHO)|
|Molar mass||149.233 g/mol|
Phentermine, a contraction of "phenyl-tertiary-butylamine", is a psychostimulant drug of the substituted amphetamine chemical classes, with pharmacology similar to amphetamine. It is used medically as an appetite suppressant.
Phentermine is approved in Australia as an appetite suppressant and is medically prescribed as a diet pill; intended for obese patients and patients that are considered a medical risk due to weight. Phentermine is a prescription that helps aid weight-loss and is designed for short-term use with a combination of exercise and a healthy diet.
In the USA, phentermine is FDA approved, and is currently being studied in combination with other medications for obesity. The first such combination is the appetite suppressant phentermine/topiramate (Qsymia, formerly Qnexa). In 2012, the FDA approved its sale in the United States.
There are various phentermine brands and supplements available through tablets, capsules, and drinks such as: Vites, Adipex and Qsymia available in various dosages. Phentermine tablets or capsules are manufactured by generic pharmaceutical groups.
Generally, phentermine appears to be relatively well tolerated.
Common (>1% incidence) adverse effects include:
- Xerostomia (dry mouth)
- Urinary frequency
- Facial oedema
- Unpleasant taste
- Changes in libido
- Aortic regurgitation
- have had a known hypersensitivity or idiosyncratic reaction to sympathomimetic amines.
- are taking another amphetamine pharmaceutical (i.e., racemic amphetamine, Adderall, dextroamphetamine, or lisdexamfetamine), methamphetamine, dexfenfluramine, fenfluramine, furazolidone, guanadrel, guanethidine, or have taken a monoamine oxidase inhibitor (MAOI) (e.g., phenelzine) in the last 14 days.
- have hyperthyroidism, glaucoma, peptic ulcers, prostatic hypertrophy, or epilepsy.
- are receiving treatment with drugs that increase blood pressure.
- currently have heart disease (e.g. advanced arteriosclerosis, pulmonary hypertension, uncontrolled hypertension, arrhythmias) or cerebrovascular disease (e.g., stroke).
- are pregnant, planning to become pregnant, or breast-feeding.
- are receiving serotonergic medications, such as selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and tricyclic antidepressants, due to the potential for serotonin syndrome to be precipitated by the cotreatment.
Medicines which may interact with phentermine, such as dexfenfluramine, fenfluramine, furazolidone, or MAOIs (e.g., phenelzine) are contraindicated because of the risk of serious side effects, such as increasing headache, high blood pressure, slow heart rate, elevated temperature, or possibly fatal lung problems, may be increased. Guanadrel (Hylorel) or guanethidine (Ismelin) effectiveness may be decreased by phentermine. Antacids may decrease the excretion of phentermine. Carbonic anhydrase inhibitors (acetazolamide, dichlorphenamide, methazolamide) may decrease the excretion of phentermine.
Mechanism of action
Phentermine has some similarity in its pharmacodynamics with its parent compound, amphetamine, as they both are TAAR1 agonists, where the activation of TAAR1 in monoamine neurons facilitates the efflux or, release into the synapse, of these neurochemicals; at clinically relevant doses, phentermine primarily acts as a releasing agent of norepinephrine in neurons, although, to a lesser extent, it releases dopamine and serotonin into synapses as well. Phentermine may also trigger the release of monoamines from VMAT2, which is a common pharmacodynamic effect among substituted amphetamines. The primary mechanism of phentermine's action in treating obesity is the reduction of hunger perception, which is a cognitive process mediated primarily through several nuclei within the hypothalamus (in particular, the lateral hypothalamic nucleus, arcuate nucleus, and ventromedial nucleus). Outside the brain, phentermine releases norepinephrine and epinephrine – also known as noradrenaline and adrenaline respectively – causing fat cells to break down stored fat as well.
In 1959, phentermine first received approval from the United States FDA as an appetite-suppressing drug. Phentermine hydrochloride then became available in the early 1970s. It was previously sold as Fastin from King Pharmaceuticals for SmithKline Beecham, but in 1998, it was removed from the market. Medeva Pharmaceuticals sells the name brand of phentermine called Ionamin and Gate Pharmaceuticals sells it as Adipex-P. Phentermine is also currently sold as a generic.
Phentermine was marketed with fenfluramine as a combination appetite suppressant and fat burning agent under the popular name Fen-Phen. In 1997, after 24 cases of heart valve disease in Fen-Phen users, fenfluramine and dexfenfluramine were voluntarily taken off the market at the request of the FDA. Studies later proved nearly 30% of people taking fenfluramine or dexfenfluramine had abnormal valve findings.
Phentermine is still available by itself in most countries, including the US. However, because it is similar to amphetamine, it is classified as a controlled substance in many countries. Internationally, phentermine is a schedule IV drug under the Convention on Psychotropic Substances. In the United States, it is classified as a Schedule IV controlled substance under the Controlled Substances Act. In contrast, amphetamine preparations are classified as Schedule II controlled substances.
Phentermine is being studied in combination with other medications for obesity. The first such combination is the appetite suppressant phentermine/topiramate (Qsymia formerly Qnexa). In 2012, the FDA approved its sale in the United States.
- Acxion (MX)
- Adipex P (immediate release)
- Adiphene (India)
- Ionamin (slow-release resin, Australia, discontinued in the US)
- Duromine (slow-release resin, New Zealand, Australia and South Africa)
- Metermine (slow-release resin, Australia)
- PhenObestin 37.5
- Pro-Fast SA
- Qsymia (with topiramate)
- Razin (Israel)
- Phentermine Trenker
- Sinpet (MX)
- Supremin (PH)
- Suprenza (orally disintegrating tablet)
- Umine (NZ)
- Weltmine (KP)
- Benzaldehyde and 2-nitropropane are cross-reacted in a variant of the Henry reaction
- The nitro group is reduced with hydrogen gas over Raney nickel catalyst
- The hydroxyl group is chlorinated with thionyl chloride to yield 2-amino-1-chloro-2-methyl-1-phenylpropane
- This is reduced with hydrogen gas over a palladium on magnesium glycinate catalyst to yield the product, phentermine
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we confirmed agonistic activity at human TAAR1 of several other compounds, including the trace amines octopamine and tryptamine, the amphetamine derivatives l-amphetamine, d-methamphetamine, (+)-MDMA, and phentermine, and the catecholamine metabolites 3-MT and 4-MT (Bunzow et al., 2001; Lindemann and Hoener, 2005; Reese et al., 2007; Wainscott et al., 2007; Wolinsky et al., 2007; Xie and Miller, 2007; Xie et al., 2007).
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- U.S. Patent 2,408,345
- U.S. Patent 2,590,079